Oropharynx

Men with throat cancer will soon outnumber women with cervical cancer In The US

Source: www.houstonpublicmedia.org
Author: Carrie Feibel

The national increase in cases of oropharyngeal cancer related to the human papilloma virus is troubling, because there is no screening test to catch it early, like the Pap test for cervical cancer.

The oropharynx is the area of the throat behind the mouth, and includes the tonsils and the base of the tongue. Oropharyngeal cancer is increasing in both men and women, but for reasons that aren’t well understood, male patients are outnumbering female patients by five to one, according to Dr. Erich Sturgis, a head and neck surgeon at MD Anderson Cancer Center.

“It’s usually a man, and he notices it when he’s shaving. He notices a lump there,” Sturgis said. “That lump is actually the spread of the cancer from the tonsil or the base of the tongue to a lymph node. That means it’s already stage three at least.”

In the U.S., the number of oropharyngeal cancers caused by HPV are predicted to exceed the number of cervical cancers by 2020, Stugis said.

“With cervical cancer, we’ve seen declining numbers well before we had vaccination, and that’s due to the Pap smear being introduced back in the late 50s,” he said. “But we don’t have a screening mechanism for pharynx cancer.”

Research on an effective screening test for early-stage pharynx cancer is still underway. The reasons for the disproportionate effect on men are unknown. One theory is that people are engaging in more oral sex, but that doesn’t explain why men are more affected than women. Some suspect hormonal differences between men and women may be involved, and others hypothesize that it takes longer for women to “clear” the viral infection from their genitals, compared to men, according to Sturgis.

One of Sturgis’s patients, Bert Noojin, is an attorney in Alabama. He felt a little knot in his neck in early 2011. It took three trips to his primary care doctor, then a visit with an otolaryngologist before he was referred for a biopsy. Noojin was diagnosed with oropharyngeal cancer, but he still felt fine.

“It was still hard for me to believe I was sick in any way,” he recalled. “I didn’t even have a serious sore throat.”

After being diagnosed, Noojin came to MD Anderson Cancer Center in Houston for a second opinion and to pursue treatment. It was less than three months from when he first felt the knot, but an oncologist warned him the cancer was spreading fast.
“He said ‘Well, you need to start treatment right away’ and I said, ‘Well, do I have a week or 10 days to go home and get some things in order?’ and he said ‘No.’”

“He said ‘If you leave here, and you’re not part of our treatment plan when you leave here, I don’t think we’ll be able to help you.’ That is how far this disease had progressed, in such a very short time.”

The prognosis for HPV-related oropharyngeal cancer is good, especially compared to patients whose throat cancer is caused by heavy use of tobacco or alcohol, according to Sturgis. Between 75 and 80 percent of patients with the HPV-related type survive more than five years.

But the treatment is difficult, and can include “long-term swallowing problems, long-term problems with carotid artery narrowing, and long-term troubles with the teeth and jaw bone, and things that can cause a need for major surgeries later.”

In the summer of 2011, Noojin began chemotherapy and radiation at MD Anderson. He struggled with pain, nausea, and swallowing, and had to get a temporary feeding tube.

“Your throat just shuts down,” he said. “You’re burned on the inside. Just swallowing your own saliva, as an instinct, hurts.”

Noojin lost 45 pounds during treatment but feels lucky to have survived. He went back to his law practice in Alabama.

Noojin learned that cancers related to HPV, which is sexually transmitted, are cloaked in shame and guilt.

He experienced this first-hand when his marriage fell apart during his recovery. His wife was traumatized by the difficult months of treatment, he said. In addition, she irrationally blamed herself for giving him the virus, even though he was probably exposed many years earlier. He tried to comfort her and dispel her guilt, but they eventually divorced.

“I was married over two decades, but I was married previously, and she was married previously,” he said. “It just makes no sense for any of this to have a stigma.”

An estimated 80 percent of America women and 90 percent of men contract HPV at some point in their lives, usually when they’re young and first become sexually active. But the cancers caused by HPV can take years to develop.

“It’s a virus. It’s not anybody’s fault,” Noojin said.

He echoed the public health experts in calling for an end to the silence and shame, and a shift to a focus on prevention.

“All of what I went through, and all of what hundreds of thousands of men, and women, because of cervical cancer – what they have gone through is avoidable for the next many generations … if we just got serious about making sure our kids get vaccinated.”

The series of three shots can be given as early as age nine, but must be completed before the age of 26 to be effective. Currently, the completion rate for young women in the U.S. is less than 50 percent. Among young men, it’s less than 30 percent. That’s why experts warn these particular cancers will still be a problem decades from now.

September, 2016|Oral Cancer News|

Immunotherapy Continues to Advance in Head and Neck Cancer

Source: www.onclive.com
Author: Megan Garlapow, PhD
 

Concomitant administration of motolimod with cetuximab (Erbitux) increases the innate and adaptive immune response in the blood and the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC), overcoming negative prognostic biomarkers of cetuximab therapy alone, according to the biomarker data from a recent phase Ib clinical trial that was presented at the 2016 Head and Neck Cancer Symposium. The trial was recently amended to add nivolumab to the combination of cetuximab and motolimod.

Robert-FerrisDr. Robert Ferris, MD PhD

 

“We know that PD-1 and PD-L1 are overexpressed in head and neck cancer, and so it was somewhat irresistible to combine our baseline treatment of cetuximab and motolimod with the PD-L1 inhibition pathway. EGFR itself drives PD-L1, so combining cetuximab with anti-PD-1 inhibitor makes sense. So, we’ve amended this trial. We’re now accruing to treatment with cetuximab, motolimod, and the anti–PD-L1 nivolumab in this trial,” said lead author Robert Ferris, MD, PhD, professor, Departments of Otolaryngology, Radiation Oncology, and Immunology, Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

According to the authors of the phase Ib data presented at the symposium, the rationale for combining cetuximab with motolimod (VTX2337) as neoadjuvant therapy was that cetuximab induces cellular immunity that correlates with neoadjuvant clinical response. The phase I dose-escalation and safety of the combination had been established (NCT 01334177).

This study of neoadjuvant cetuximab and motolimod had accrued 14 patients with HNSCC that was stage II-IV, resectable, and located in the oropharynx, oral cavity, hypopharynx, or larynx. These patients were biopsied, treated with cetuximab and motolimod for 4 weeks, and then underwent surgery. The endpoints of the trial were the modulation of immune biomarkers.

Interferon-inducible cytokine IP-10 increased after the patients were administered neoadjuvant cetuximab and motolimod (P = .0001). After the neoadjuvant treatment, the peripheral blood lymphocytes had an increased frequency of EGFR-specific CD8 T cells. After the neoadjuvant treatment, regulatory T cells had decreased suppressive receptors and transforming growth factor-β, which induces Foxp3. Also, after the neoadjuvant treatment, circulating MDSCs had decreased PD-L1 (P <.07) and macrophages had increased CD16 expression (P <.07).

After the neoadjuvant treatment with cetuximab and motolimod, genotyping of T-cell receptors showed increased clonality in peripheral blood lymphocytes (P = .003 by Wilcox signed rank test) and tumor-infiltrating lymphocytes (P = .081 by Wilcox signed rank test). Most patients are more oligoclonal than healthy individuals, and some are very clonal with highly prominent expanded clones. Genotyping of T-cell receptors found that clonality was increased by the combination of cetuximab and motolimod compared with treatment with cetuximab alone.

Recent studies have indicated that the PD-1/PD-L1 pathway is upregulated in the HNSCC microenvironment, and that EGFR blockade prevents interferon-γ-mediated upregulation of PD-L1. Thus, this study has been amended to add nivolumab to the adjuvant treatment with cetuximab and motolimod. The endpoints are still the modulation of immune biomarkers.

The aim is to target the tumor microenvironment, such that tumor immune escape is reversed and T cells eliminate HNSCC. Antitumor T cells are reprogrammed to reverse inhibitory signals. Combining the toll-like receptor agonist, motolimod, with cetuximab and with PD-1 pathway inhibitors, such as nivolumab, may enhance the priming and activity of T cells.

“Targeting the tumor microenvironment requires understanding as well as reversal of immune escape mechanisms in the cellular compartment. Reprogramming antitumor T cells to reverse inhibitory signals can be done by directly disrupting those inhibitory signals, the so-called checkpoint receptor field, and can be done potentially by combining proinflammatory signals, such as toll-like receptor agonists, to chemo-attract cells into the microenvironment and to create good inflammation to overcome suppressive factors,” said Ferris.

Recent findings have shown tremendous promise for nivolumab in head and neck cancer. Bristol-Myers Squibb (BMS) announced in January 2016 that nivolumab improved overall survival versus investigator’s choice of therapy for patients with platinum-refractory squamous cell carcinoma of the head and neck in the phase III CheckMate-141 trial. Findings from the study are being discussed with the FDA and other health authorities, according to BMS.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
February, 2016|Oral Cancer News|

Prognosis of tumors positive for human papilloma virus in head and neck cancers varies according to the site

Source: www.sciencecodex.com
Author: staff

Patients with cancer of the throat and who are positive for the Human Papilloma virus (HPV+) have a good prognosis, but until now the effect of being HPV+ on the prognosis of tumours located elsewhere in the head and neck was unknown. Danish researchers have now shown that HPV status appears to have no prognostic effect on the outcome of primary radiotherapy in head and neck cancer outside the oropharynx (the part of the throat located behind the mouth, and which contains the soft palate and the base of the tongue), the ESTRO 33 congress will hear today (Sunday).

Presenting her results to the congress, Dr Pernille Lassen, MD, PhD, from the Aarhus University Hospital, Aarhus, Denmark, will say that head and neck cancers located outside the oropharynx should probably not be treated with the less intensive treatment strategies that are currently being investigated in clinical trials for HPV+ oropharyngeal tumours.

“HPV status has a very potent prognostic impact in radiotherapy for oropharyngeal cancer, and DNA from HPV has been found in all types of head and neck cancer, although it is far more common in oropharyngeal tumours. We decided to investigate the impact of HPV status in non-oropharyngeal cancers in the DAHANCA database, which includes all Danish head and neck cancer patients,” Dr Lassen will say.

The researchers searched the database to identify patients with locally advanced cancers who had been treated primarily with radiotherapy, and identified 1606 patients with larynx and pharynx carcinomas. Overall, 40% of the tumours were HPV positive, and the frequency was significantly higher in oropharyngeal cancer (57%), than in non-oropharyngeal (13%).

Being positive for HPV significantly improved tumour control (81% as opposed to 55%), as well as survival from the cancer (89% and 55% respectively), and death from any cause (82% and 38% respectively), after five years.

“In non-oropharyngeal cancers we found no prognostic impact of being HPV positive in any of these endpoints,” Dr Lassen will say. “This indicates that HPV status does not help us in predicting response to treatment, and hence the outcome of these cancers.

“We know from laboratory studies that HPV positive tumour cells are much more sensitive to radiation therapy than HPV negative cells, so until now we believed that they would behave similarly irrespective of site,” Dr Lassen will say. “However, these data indicate that this is not the case, and at present we do not understand why this should be, though it probably can be ascribed to other biological/genetic differences between the tumours rather than the HPV status. We would now like to try to elucidate the underlying mechanisms behind these different outcomes.”

There could be, for example, biological and/or genetic differences between the tumours other than the HPV status, the researchers say; for example, genetic changes caused by smoking tobacco, differences due to tumours of mixed make-up (for example, a combination of HPV+ and tobacco), or perhaps simply differences due to the site. “Such tumours with a combination of causes represent a challenge in our clinical daily practice,” Dr Lassen will say.

“We have started following up our work by analysing all the tumour samples using polymerase chain reaction, a way of amplifying DNA in order to be able to analyse changes in genetic information. We hope this will enable us to understand more about why the role of HPV in non-oropharyngeal tumours is so different. There are few data available on this subject at present, so finding out will be an important step towards optimising treatment for these patients.”

President of ESTRO, Professor Vincenzo Valentini, a radiation oncologist at the Policlinico Universitario A. Gemelli, Rome, Italy, commented: “These findings will have an important impact on the treatment of HPV+ head and neck cancers, and are likely to lead to a change in current practice.”

Source: European Society for Radiotherapy and Oncology (ESTRO)

April, 2014|Oral Cancer News|

Global trends in oral cancers

Source: www.dailyrx.com
Author: staff

It used to be that smoking and drinking alcohol were the biggest risk factors for cancers that develop in the mouth and throat. Those trends may be changing, according to a new study. That new study uncovered that cancers that appear in the throat right behind the mouth have increased, primarily in developed countries. The trend has been most prevalent in men under the age of 60, the researchers found. These increases, the authors suggested, may be linked to human papillomavirus (HPV), a sexually transmitted virus that’s associated with a number of cancers, including oral cancers.

Anil K. Chaturvedi, PhD, of the National Cancer Institute, led this study that examined incidence trends for oropharyngeal (part of the throat behind the mouth) and oral cavity (mouth) cancers in 23 countries across four continents. The researchers examined the countries’ cancer registry data for the years 1983 to 2002.

In the study’s introduction, the authors noted that oral cavity cancers (OCC) have declined recently in most parts of the world due to the declines in tobacco use. At the same time, oropharyngeal cancers (OPC) have risen over the past 20 years in some countries. OPC rates were compared to those of OCC and lung cancers to distinguish the potential role of HPV from smoking-related cancer trends.

The researchers tracked specific OPC sites, including base of the tongue, tonsils, oropharynx and pharynx (throat). OCC sites included the tongue, gums, floor of the mouth, palate (roof of the mouth) and other areas of the mouth.

Here’s what the researchers learned:

  • OPC increased significantly among men in the United States, Australia, Canada, Japan and Slovakia. Incidence trends for OCC in these countries were either not significant or there was a significant decline in OCC.
  • Among women, there was an increase in both OPC and OCC cases in Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland and the United Kingdom.
  • In Denmark and the United Kingdon, both OPC and OCC increased significantly, with stronger increases seen in OPC than in OCC.
  • Increasing OPC incidence in men was accompanied by decreasing incidence in lung cancer.
  • For women, however, increasing OPC incidence occurred at the same time as increasing Lung Cancer incidence.
  • OPC incidence rose substantially more for younger men under the age of 60 than in older ages in the United States, Australia, Canada, Slovakia, Denmark and the United Kingdom.
  • For OCC, a similar statistically significant increase at younger ages was seen only in the United Kingdom, while OCC incidence decreased significantly at younger ages in the United States, Australia and Canada.

The authors of this study pointed out that recent research has suggested that about 60 to 70 percent of OPCs in the US are caused by HPV infection, compared with less than 10 percent in less economically developed areas. The researchers wrote, “Our results underscore the potential for increasing global relevance of HPV as a cause of OPC.”

They added that the reasons for higher increases seen in men are not clear and warrant more investigation.

“This male predominance also has important implications for male HPV vaccination policy in several countries,” according to the researchers.

Meanwhile, tobacco and alcohol use remain major risk factors for both OPC and OCC, with OCC incidence two to four times higher than OPC in most parts of the world, “…underscoring the need for prevention strategies targeted toward tobacco and alcohol use,” the authors concluded.

Note:

1. This study was published November 18 in the Journal of Clinical Oncology.
2. The research was supported by the National Cancer Institute and by a grant from the Institut National du Cancer.
3. One of the authors disclosed financial ties with two pharmaceutical companies.

November, 2013|Oral Cancer News|

Nutritional and Zinc Status of Head and Neck Cancer Patients: An Interpretive Review

Source: Journal of the American College of Nutrition
Authors: Ananda S. Prasad, MD, PhD, MACN, Frances W.J. Beck, PhD, Timothy D. Doerr, MD, Falah H. Shamsa, PhD, Hayward S. Penny, MS, RD, Steven C. Marks, MD, Joseph Kaplan, MD, Omer Kucuk, MD and Robert H. Mathog, MD

 

Abstract

In this review, we provide evidence based on our studies, for zinc deficiency and cell mediated immune disorders, and the effects of protein and zinc status on clinical morbidities in patients with head and neck cancer. We investigated subjects with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. Patients with metastatic disease and with severe co-morbidity were excluded. Nutritional assessment included dietary history, body composition, and prognostic nutritional index (PNI) determination. Zinc status was determined by zinc assay in plasma, lymphocytes, and granulocytes. Pretreatment zinc status and nutritional status were correlated with clinical outcomes in 47 patients. Assessment of immune functions included production of TH1 and TH2 cytokines, T cell subpopulations and cutaneous delayed hypersensitivity reaction to common antigens.

At baseline approximately 50% of our subjects were zinc-deficient based on cellular zinc criteria and had decreased production of TH1 cytokines but not TH2 cytokines, decreased NK cell lytic activity and decreased proportion of CD4+ CD45RA+ cells in the peripheral blood. The tumor size and overall stage of the disease correlated with baseline zinc status but not with PNI, alcohol intake, or smoking. Zinc deficiency was associated with increased unplanned hospitalizations. The disease-free interval was highest for the group which had both zinc sufficient and nutrition sufficient status.

Zinc deficiency and cell mediated immune dysfunctions were frequently present in patients with head and neck cancer when seen initially. Zinc deficiency resulted in an imbalance of TH1 and TH2 functions. Zinc deficiency was associated with increased tumor size, overall stage of the cancer and increased unplanned hospitalizations. These observations have broad implications in the management of patients with head and neck cancer.

 
The following news story is scientifically tied together with the study above; one explains the other. Please follow this link to read the study titled: 
Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFκB, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line

 http://oralcancernews.org/wp/?p=14853

 

* This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

 

July, 2013|Oral Cancer News|

The New Face of Oral Cancer

Source: nursing.advanceweb.com
By Jonathan Bassett
Posted on: April 22, 2013
 
 

For decades tobacco was the primary cause of oral cancer but a more insidious culprit has emerged. 

Jerry Wilck had no reason to suspect anything. Why would he? He only smoked for a couple of years and gave it up more than 40 years ago. He didn’t drink excessively, didn’t have a family history of cancer, and took good care of himself.

In fact, maybe the only reason the 59-year-old consulted an oral surgeon about the small sore on his tongue – the result of a habit of running this particular spot along his teeth – was that there happened to be such a specialist right there in his office.
Wilck was a general practice dentist in Langhorne, Pa., and particularly attuned to anomalies of the soft tissues of the mouth. His oral surgeon took no chances and ordered a biopsy.

Wilck was “floored” the night in March 2005 when the lab report arrived by fax from the oral pathology department at Temple University in Philadelphia – squamous cell carcinoma.

Wilck immediately consulted with John Ridge, MD, PhD, FACS, chief of head and neck surgery at Temple’s Fox Chase Cancer Center. After surgical removal of part of his tongue and lymph nodes from his neck, along with a round of physical and speech therapy, Wilck is now cancer free and has full use of his jaw, throat and voice.

“I was lucky,” confessed Wilck, who retired from practice in 2009 and now spends a large part of his time speaking to dental students, advocacy groups and the media about the dangers of oral cancers. “The surgery was successful and I didn’t need radiation or chemotherapy. A lot of people in other lines of work might have ignored the symptoms. My story could have ended very differently.”

 

Under the Radar

Wilck was one of the fortunate cases caught early and treated effectively.

Oral cancer, along with cancers of the head and neck, respond well to treatment when detected early in their development, explained Dong Moon Shin, MD, FACP, Frances Kelly Blomeyer Chair in Cancer Research and professor of hematology, medical oncology and otolaryngology at Emory University School of Medicine in Atlanta.

A leading researcher in the field of oral cancer, Shin has authored more than 220 peer-reviewed articles and is principal investigator of Emory’s National Cancer Institute-funded Head and Neck Cancer Specialized Program of Research Excellence (SPORE), an interdisciplinary research collaborative on the forefront of discovering treatments and preventive measures for these cancers, along with other NCI-funded research programs.

Shin’s current research directions center on prevention with natural compounds (including green tea and cancer-fighting agents found naturally in vegetables), along with anti-cancer drug delivery with nanotechnology – using nanometer-sized particles with novel properties engineered for the targeted delivery of anticancer drugs into cancer cells, while sparing healthy cells. Such “smartly” formulated nanoparticles carrying anti-cancer drugs can be specifically delivered to the cancer cells, thus minimizing side effects and maximizing the anti-cancer activity of the drugs, explained Shin. “Nanotechnology has the potential to revolutionize cancer care.”

Despite these encouraging research avenues, oral cancer is a specialty area deserving of more physicians and scientists such as Shin devoted to it, said Terry Day, MD, FACS, director of the division of head and neck oncologic surgery and the Head and Neck Tumor Center at Hollings Cancer Center at the Medical University of South Carolina in Charleston.

 

What You Need to Know about Oral Cancer: 

Christine Brader an oral cancer activist who has survived three bouts with the disease.

Archive ImageA

While oral cancer kills almost three times as many people as cervical cancer – one person dies every hour of every day from the disease, according to the Oral Cancer Foundation – it often receives less attention than more recognizable forms such as cancer of the skin or lungs.

“During my medical school training I began to see that these patients often had nowhere to turn,” said Day of the dearth of qualified specialists. He decided to make it his career’s mission to treat this complex, disabling, and potentially deadly subgroup of oncology.

“To look in the mirror and not recognize the person looking back at you – it’s shocking,” said Christine Brader, 49, an oral cancer activist who has survived three bouts with the disease. “I couldn’t believe it was me. Children would be scared of me out in public. I looked like a monster.”

 

Complex Complications

After “too many surgeries to count,” including the removal of her teeth and half of her jaw, implantation of a titanium plate (which her body rejected), and radiation and chemotherapy, Brader is now cancer free and maintains the use of her voice.

But it wasn’t an easy road. Oral cancer affects everything, said Brader – the way you look, the way you speak, your ability to eat and swallow. She spent two weeks in a medically induced coma, months in the hospital, and a grueling year-long recovery to get where she is today. She had to give up her job, her dogs, and her beloved home in Lehighton, Pa. The single mother of two had no caregiver to depend on, making the treatments even harder to get through.

“This is different than breast cancer and [cancer of] the internal organs,” said Brader, who is now independent but lives with many aftereffects and tires easily. “There’s no hiding it with clothing.”

She spends much of her time volunteering for the Oral Cancer Foundation’s public forum, helping new members and speaking at awareness events. She speaks to young people and the media regarding the dangers of smoking and chewing tobacco. She shares her story freely with the media, attends oral cancer screening events and volunteers for anti-smoking groups. She appeared in a TV commercial for Truth, a national anti-smoking prevention campaign, and the CDC’s Tips From Former Smokers Campaign.

“I try to make a difference,” Brader said. “I tell young people, ‘if someone you know starts smoking, be a friend and try to help them quit.’ It could save their life. By never starting to smoke, you never have to quit.”

 

Emergence of HPV

Brader began smoking as a teenager as a result of peer pressure, and continued the habit throughout her life. Her journey with oral cancer represents the traditional path – for decades, oral cancer was a disease of lifelong tobacco users that showed up later in life.

Fortunately, patient education regarding the riskiness of smoking, chewing tobacco and alcohol abuse has lowered the incidence of oral cancers from those origins, said Day.

However, a new contributing factor has moved into its place – human papilloma virus number 16 (HPV16). HPV16 is a common sexually transferred virus that is also responsible for the majority of cervical cancers in women. It’s now responsible for about 52% of newly diagnosed patients with oral and oropharyngeal cancer, according to the Oral Cancer Foundation.

The emergence of HPV16 as a risk factor has changed the demographic of oral cancers in the U.S. The disease is trending younger; the fastest growing segment of the oropharyngeal cancer population is those between the ages of 25 and 50, said Day. This is primarily due to HPV16, and cancers from this origin typically occur in the area of the throat behind the mouth, in the oropharynx, tonsils, and at the base of the tongue.

It also means oral and oropharyngeal cancers can strike in subtle silence; when in years past, a history of smoking or using chewing tobacco might prompt primary care physicians and their patients to be more diligent in screenings, HPV is a silent invader that can display little or no symptoms until it’s too late.

“HPV is definitely the coming epidemic in oral cancer,” said Brian Hill, a stage four oral cancer survivor and founder of the Oral Cancer Foundation. Hill had never used tobacco and his cancer – of an HPV16 etiology – was detected after bilaterally metastasizing and progressing into his cervical lymph nodes.

“My own journey included radiation and surgery, back in the days before IMRT [intensity modulated radiation therapy], and a very difficult and protracted recovery with significant quality of life issues, now a decade out,” Hill said.

 

Partners in Prevention

For Day, the ideal strategy to get a handle on the disconcerting mortality rates associated with oral cancer arises from a partnership between primary care physicians and dental professionals providing routine screenings for early-stage symptoms and swiftly referring to specialists.

Survival rates after early detection (stages 1 and 2) can be 80%-90%, while survival rates of late-stage detections (after the disease has advanced to stage 3 and 4) fall to 40%-50%, said Shin.

Head and neck screenings for cancer are relatively simple, painless, two- to three-minute visual and tactile exams performed in the dentist’s office, said Seung-Hee Rhee, DDS, FAGD, a general practice and cosmetic dentist in New York City, and spokesperson for the Academy of General Dentistry.

“You’re looking for any asymmetries, sores that don’t heal, abnormal lesions that seem suspect,” said Rhee, who makes these screenings part of her regular dental exams along with obtaining a thorough patient history to uncover potential signs and risk factors before they become major problems.

And new technology is making these screenings even easier for dentists, explained Rhee. Handheld blue-spectrum light emitters such as the Velscope shined inside the mouth will illuminate soft tissue abnormalities in different patterns than healthy tissue. This can aid dentists in detecting cancers even before they can be picked up by the unassisted eye.

“Early detection is where we’ll make a difference,” said Rhee. “[Dentists] are often the first line of defense.” She adds that HPV vaccinations for cervical cancer administered in the pre-teen years are another potential course of action being studied to help prevent these diseases. The Oral Cancer Foundation supports the use of the HPV vaccine for its potential in reducing the incidence of oral cancer, though the FDA currently prohibits drug manufacturers from making this specific claim.

“We highly encourage people who have precancerous lesions in the oral cavity or voice box [to] participate in clinical trials of chemoprevention to block the progression to invasive cancer,” said Shin.

 

Spreading the Word

While dental professionals work on the front lines to detect cases early, and researchers work tirelessly to unearth promising new treatments,

Wilck, Brader and a small army of former patients and activists travel the country speaking to schools, community groups and media outlets to underscore the importance of avoiding risk factors and receiving periodic screenings.

To mark Oral Cancer Awareness Month, the Oral Cancer Foundation is teaming with dental offices nationwide to offer free oral cancer screenings throughout April. Over 1200 free screening events are taking place in dental offices across America. A list is viewable at www.oralcancer-screening.org/events/.

The Head and Neck Cancer Alliance this year sponsored the 16th annual Oral Head and Neck Cancer Awareness Week April 14-20, said Day, who serves as president of the HNCA. This weeklong series of events promotes awareness and offers free screenings. Details are at http://www.ohancaw.com/.

“Reducing the high death rate associated with oral cancer is a tangible opportunity today,” said Hill. “We do need increased public awareness, coupled with an engaged professional dental and medical community doing opportunistic screenings.”

“My role these days is to keep people from taking the same path I did,” said Wilck. “If I reach just one person, it’s been worth it.”

 

 

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy. 

 

Researchers Investigate A Less Toxic Radiation Treatment For HPV-Positive Oropharynx Cancer

Source : Biocompare
Posted: June 03, 2013 

 

CHICAGO, IL (May 29, 2013)—Researchers from Fox Chase Cancer Center and other institutions have completed a phase II clinical trial that may help identify those patients with HPV-positive oropharyngeal cancer who do not require the full radiation dose given in a standard regimen of Intensity-Modulated Radiation Therapy (IMRT). Preliminary findings will be presented by Shanthi Marur, first author on the study and an oncologist at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, at the 49th Annual Meeting of the American Society of Clinical Oncology on Sunday, June 2.

Patients enrolled in the trial received an initial regimen of chemotherapy followed by treatment with the targeted therapy cetuximab, a monoclonal antibody. In the study, a patient’s response to those initial treatments determined the dose during radiation treatment.

“Those patients who had a really good response to chemotherapy might also be more responsive to radiation,” says Barbara Burtness, senior author on the study and chief of head and neck medical oncology at Fox Chase. “Therefore, the use of a full dose of radiation for those patients might represent overtreatment.”

Burtness is also chair of the Eastern Cooperative Oncology Group (ECOG), which sponsors this ongoing trial. ECOG is a a National Cancer Institute-funded team of researchers who organize and carry out clinical trials.

According to the National Cancer Institute, more than 40,000 people will be diagnosed with cancer of the oropharynx—a swath of tissue at the back of the throat—in 2013, and nearly 8,000 will die from the disease. Between 60 and 80 percent of cases are associated with infection by Human Papilloma Viruses, or HPVs.

“Patients with HPV-associated oropharyngeal cancer tend to be younger than other oropharyngeal cancer patients, and would be living with the aftereffects of treatment for more years,” says Burtness. A patient who undergoes standard radiation to the back of the throat—usually between 66 and 70 Gy—may suffer serious side effects like dry mouth and disfunction in swallowing.

The investigators suspected a subset of HPV-associated oropharyngeal cancer patients, identified by their response to chemotherapy, may be suitable for trials of lower radiation.

Burtness and her co-investigators enrolled 90 patients in the trial, 80 of whom were analyzable. Of those patients, 95 percent were men, and the median age was 57. The researchers reported that most patients tolerated the induction chemotherapy and treatment with cetuximab, and 96 percent completed all three cycles. Forty-six patients had a complete clinical response, which meant all signs of the primary tumor had disappeared following treatment. These patients went on to receive a lower-than-standard dose of radiation, at 54 Gy.

The researchers report that most patients tolerated the treatment with low incidence of high-grade side effects, but other data are premature. The primary endpoint of the study is two-year progression-free survival, the fraction of patients whose diseases have not worsened after two years. The investigators say that if the two-year progression-free survival rate is at least 85 percent, further studies on lower-dose radiation are warranted.

“We do not expect that anyone would want to lower the dose of radiation based on this study, which is very much a developmental study,” says Burtness. “We’ve never had a comparative trial of low dose versus standard dose IMRT.”

Burtness notes among patients who received a lower dose of radiation, “what seemed to predict for a slightly worse outcome was either a heavy smoking history (more than 10 pack years), or those with larger tumors.”

She says that although it’s too early to draw definitive conclusions, the early results “may justify further study of deintensifying radiation among nonsmokers with HPV-associated oropharyngeal cancers.”

In addition to Burtness and Marur, other investigators include Christine H. Chung at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, MD; David R. Trevarthen at the Swedish Medical Center in Denver; Shuli Li at the Dana-Farber Cancer Institute in Boston, MA; Weiqiang J. Zhao and Maura Gillison at the Ohio State University College of Medicine in Columbus, OH; Alexander D. Colevas at the Stanford Cancer Center in Stanford, Calif.;  Anthony J. Cmelak at the Vanderbilt-Ingram Cancer Center in Nashville, TN; Julie E. Bauman at the University of Pittsburgh Medical Center, PA; Lynne I. Wagner at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, IL; Balkrishna N. Jahagirdar at HealthPartners and Regions Cancer Care Center in St. Paul, MN; William H. Westra at the Johns Hopkins Hospital in Baltimore, MD; Robert Ferris at the University of Pittsburgh Cancer Institute, PA. The study is sponsored by ECOG.

 

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

 

 

 
June, 2013|Oral Cancer News|

When a virus causes cancer, surgical robot can help

Source: www.bizjournals.com
Author: James Ritchie

Dr. Keith Wilson finds robotic surgery to be a good approach for removing tumors growing deep in the throat, as I recently reported. As it turns out, such tumors are often part of an alarming trend. They’re often caused by the sexually transmitted human papillomavirus, also known as HPV.

In decades gone by, oral cancer was almost always associated with tobacco and alcohol use. It was typically a disease of old men. No more. Many of Wilson’s patients are nonsmokers and very light drinkers.

“I can’t tell you how surprised people get,” said Wilson, who is chief of staff at University of Cincinnati Medical Center. “We’re seeing younger, more affluent and more highly educated patients.”

High-risk HPVs cause virtually all cervical cancers. They have in recent years been implicated in oropharyngeal cancers. The oropharynx is the middle part of the throat, including the soft palate, the base of the tongue and the tonsils.

About 63 percent of oropharyngeal cancers, or 11,000 cases per year, are associated with HPV infection, according to the American Dental Association. They’re frequently under age 50.

Fortunately for such patients, HPV-associated oropharyngeal cancers have a better prognosis than those with other causes. Wilson said that cure rates can approach 90 percent.

The da Vinci surgical robot is an effective tool for removing them, he said, because its long, joined arms can go where a surgeon’s hands can’t. But the machines, made by Sunnyvale, Calif.-based Intuitive Surgical Inc., are gaining some criticism. The robotic surgery system is facing safety questions from the U.S. Food and Drug Administration after a string of complaints across the country – as many as 500 since January 2012.

April: Oral Cancer Awareness Month

Source: Aspen Dental

April is Oral Cancer Awareness Month. According to Brian Hill, founder and executive director of the Oral Cancer Foundation, as many as 40,000 people in the United States will be told they have oral or pharyngeal cancer in 2012. Some of them may be sitting in your dental chair today. With one person dying of oral cancer every hour of every day, and more than 50% of those diagnosed not living more than 5 years, this is a reminder to screen every patient yourself, and encourage your dental hygiene staff to do the same.

The Statistics

About 100 people are diagnosed with oral cancer every day in the United States. Few people are aware that the death rate for oral cancer is higher than for many other types of cancers, which is because oral cancer often is not discovered until it has reached later stages. This is particularly true for human papilloma virus number 16 (HPV16)-related oral cancer, which occurs most frequently in the posterior areas of the mouth—at the base of the tongue, around the tonsils, and in the oropharynx—where it’s harder to spot without a very thorough exam. To further complicate things, HPV16-related cancer does not always present the tell-tale physical characteristics, including lesions, that are easily distinguished from healthy oral tissues. This is not good news, because HPV16 has reached epidemic levels in the United States: of the 37,000 incidences of oral cancer, about 20,000 (up to 60%) can be linked to HPV, according to Hill.

Oral cancer accounts for 85% of the cancers grouped under “head and neck” cancers. If the number of larynx cancer cases (for which the historic risk factors; tobacco and alcohol are the same) is added to the oral cancer category, we’re now talking 50,000 people diagnosed yearly and 13,500 deaths per year in this country. More than 640,000 new cases occur worldwide annually. These stats do not include brain cancer, which is its own category.

“Late discovery and misdiagnosis are the biggest problems,” Hill says. “I’m a very typical example of this.” Hill was misdiagnosed with an infection by a physician when a painless lump appeared on the side of his neck. When it had not resolved after a course of antibiotics, Hill, who had a background in dentistry, insisted on having a needle aspiration biopsy. Testing resulted in a diagnosis of HPV16-related squamous cell carcinoma, a very deadly cancer. Fourteen years after extensive surgery, and both radiation and chemotherapy, he has since heard from literally thousands of people that they were misdiagnosed more than once, told not to worry about it, or were merely given antibiotics. “Why are so many people diagnosed late?” Hill asks. “Because, according to one study,probably under 20% of dentists are performing oral screenings.” 1 Another problem is that public awareness about oral cancer, its early signs and symptoms, and its changing etiology, is low. Additionally, oral cancer has historically been linked to long-term tobacco use and high alcohol consumption (or a combination of both), with associated lesions usually seen in the anterior areas of the oral cavity. With the prevalence of HPV16-related oral cancer increasing at an alarming rate, and tobacco-related cancers on the decline, it is critical that dental and medical professionals re-educate the public to understand the current risk factors and the need for an annual professional screening.

The Impact of HPV16

It was reported in 2009, before the advent of HPV-related cancers, that oral cancer incidence rates were more than twice as high in men as in women, and both were on the decline.2 That was before HPV-infected individuals became the fastest growing segment of the oral cancer population. HPV16 is a human papillomavirus related to more than 150 other HPV versions, over 40 of which can be easily sexually transmitted.3 Nine of these are known to be cancer causing. HPV’s were directly linked to cervical cancer, also squamous cell carcinoma, which was the number one killer of women in 1948. “Using the cervical cancer model, once ‘opportunistic’ screening and PAP testing became routine, the cervical cancer death rate dropped 71% in 10 years,” Hill notes. “We have no ‘viruscide’. But we do have an HPV vaccine that can be administered before young people become sexually active.” This is important information to share with patients, because 50%-80% of Americans will have HPV in their lifetime according to the Center for Disease Control and Prevention (CDC). About half of all men and more than 3 out of 4 women will be diagnosed with it at some point.4

Detection vs Diagnosis

Signs and symptoms or oral cancer, if there are any, range from a sore area or lesion that bleeds easily, a lump or thickening of tissues in the mouth or neck, ear pain, indurations or hard spots in the mucosa, or a red or white patch or ulceration that does not resolve within 2 weeks. If any of these are evident, the patient should return within 7-14 days to confirm either persistence or resolution. Later symptoms include difficulty chewing, swallowing, and/or moving the tongue or jaws.2

Early stage (1 and 2) lesions, which may not be readily evident during a routine exam, usually are asymptomatic and often mimic other conditions.5 It is important for dentists to acknowledge that malignant and benign lesions are virtually indistinguishable clinically, and their biological relevance cannot be assessed based on their appearance.5 Most resources advise referring any persistent abnormalities to a specialist. “We have a highly defined referral system in dentistry,” Hill points out. “You don’t have to learn anything new; you don’t have to be the expert. You just have to refer suspect tissues up the professional chain for proper evaluation/biopsy. There are many kinds of oral lesions. You may see only 3 cancer cases in 20 years of practicing dentistry, but every time you find something, especially in stage 1 or 2, you have the opportunity to save a life. Dentists are the first line of defense.”

The American Cancer Society estimated in 2009 that almost 90% of oral cancers are squamous cell carcinomas, and more than 97% of these cancers occur in adults 35 years and older.5 People ranging in age from 25-50 who never smoked are the fastest growing group being diagnosed with HPV16-related oral cancer.6

Standard treatment usually involves radiation therapy and surgery, and often chemotherapy.2 Relative survival rates vary by stage at the time of diagnosis—in 2009, about 83% survived 1 year after diagnosis, 60% 5 years after diagnosis, and 49% after 10 years.2 However, today, the 5-year survival rate is only about 57% when you include all stages of the disease at time of discovery. This high death rate is directly tied to late discovery, when treatments are less effective.7 Studies reveal that oral and pharyngeal cancer are diagnosed at a localized stage in only one-third of patients in the United States.5 It’s time to make a difference.

The Oral Cancer Foundation

The Oral Cancer Foundation (OCF) is a national public service, non-profit organization dedicated to oral cancer prevention, education, research, advocacy, and patient support activities. Its website, www.oralcancerfoundation.org, provides vetted information about rates of occurrence, risk factors, signs and symptoms, treatments, current research, complications, nutrition, clinical trials, related news, links to other sources, and treatment institutions. A free, anonymous, 8700-member patient/survivor discussion forum is open to the public, providing insights and inspiration. OCF also has a free RSS oral cancer news feed you may subscribe to which is updated several times a week. OCF is a valuable resource for patients, students, and practicing medical and dental professionals.

Visit oralcancerfoundation.org to learn of its Oral Cancer Awareness Month initiatives (such as hosting a free screening event in April), and find information to share with your patients.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer

Source: Journal of Clinical Oncology

To the Editor:

In their article, Chaturvedi et al1 document the rise in human papillomavirus (HPV) –associated cancers as a proportion of squamous cell carcinomas of the oropharynx over the last 25 years. The contemporary figures are mirrored by two recent British studies2,3 demonstrating that the majority of oropharyngeal cancers are now HPV related.

In the accompanying editorial,4 Mroz et al rightly highlight the importance of evaluating HPV vaccination for both men and women in the light of these data and lament the lack of significant improvement in the outcomes for non–HPV-associated head and neck cancers. However, they also suggest that the benefit of targeting epidermal growth factor receptor (EGFR) through concurrent cetuximab may be confined to HPV-associated tumors. Although EGFR expression per se does not correlate closely with response to cetuximab, there is increasing evidence of an inverse correlation between p16INK4A expression (as a marker of HPV association) and EGFR expression shown by immunohistochemistry.5,6 Though suppressed by viral oncogenes, HPV-associated tumors retain wild-type P53,7 and patients with this tumor type have demonstrated excellent survival with existing protocols such as concurrent chemoradiotherapy or surgery with postoperative radiotherapy. Conversely, non-HPV tumors, harboring a range of mutations,8 may respond less well to DNA-damaging agents, but patients with these tumors might benefit from the addition of concurrent EGFR blockade to radiotherapy. Data from the recent SPECTRUM (Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer) study of adding another EGFR-targeting monoclonal antibody, panitumumab,9 suggest that in the metastatic setting at least, only patients with HPV-negative tumors benefit from a combination of palliative chemotherapy and an anti-EGFR strategy. If confirmed in sample sets containing non-HPV tumors treated with EGFR-targeting agents in combination with radiotherapy, this could open the door to the improvements urgently needed in HPV-negative oropharyngeal cancers, where an older demographic and greater burden of comorbidities make the uncomplicated and complete delivery of concurrent chemoradiotherapy challenging.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

March, 2012|Oral Cancer News|